n-6 Fatty acid-specific and mixed polyunsaturate dietary interventions have different effects on CHD risk: a meta-analysis of randomised controlled trials

Abstract

Randomised controlled trials (RCT) of mixedn-6 andn-3 PUFA diets, and meta-analyses of their CHD outcomes, have been considered decisive evidence in specifically advising consumption of ‘at least 5–10 % of energy asn-6 PUFA’. Here we (1) performed an extensive literature search and extracted detailed dietary and outcome data enabling a critical examination of all RCT that increased PUFA and reported relevant CHD outcomes; (2) determined if dietary interventions increasedn-6 PUFA with specificity, or increased bothn-3 andn-6 PUFA (i.e. mixedn-3/n-6 PUFA diets); (3) compared mixedn-3/n-6 PUFA ton-6 specific PUFA diets on relevant CHD outcomes in meta-analyses; (4) evaluated the potential confounding role oftrans-fatty acids (TFA).n-3 PUFA intakes were increased substantially in four of eight datasets, and then-6 PUFA linoleic acid was raised with specificity in four datasets.n-3 andn-6 PUFA replaced a combination of TFA and SFA in all eight datasets. For non-fatal myocardial infarction (MI)+CHD death, the pooled risk reduction for mixedn-3/n-6 PUFA diets was 22 % (risk ratio (RR) 0·78; 95 % CI 0·65, 0·93) compared to an increased risk of 13 % forn-6 specific PUFA diets (RR 1·13; 95 % CI 0·84, 1·53). Risk of non-fatal MI+CHD death was significantly higher inn-6 specific PUFA diets compared to mixedn-3/n-6 PUFA diets (P = 0·02). RCT that substitutedn-6 PUFA for TFA and SFA without simultaneously increasingn-3 PUFA produced an increase in risk of death that approached statistical significance (RR 1·16; 95 % CI 0·95, 1·42). Advice to specifically increasen-6 PUFA intake, based on mixedn-3/n-6 RCT data, is unlikely to provide the intended benefits, and may actually increase the risks of CHD and death.